Copper‐Catalyzed C─N Cross‐Coupling in Water Enabled by Rational Ligand Design and Micellar Cooperativity

Nitrogen-containing compounds are ubiquitous in pharmaceuticals, agrochemicals, and functional materials, and the development of sustainable methodologies for carbon-nitrogen (C─N) bond formation is of fundamental importance. Herein, we report a rationally designed bifunctional ligand and micellar cooperativity that effectively enables Cu-catalyzed amination of aryl bromides under mild aqueous conditions. A series of structurally tailored ligands was designed by systematically tuning their electronic and steric properties to stabilize the active copper catalyst and promote selective C─N bond formation. When combined with the bio-derived non-ionic surfactant CNSL-1000-M, the micellar environment provides a confined hydrophobic reaction space, enhancing catalyst performance and substrate activation. This cooperative ligand-micelle system enables the C─N coupling with both electron-rich and electron-deficient aryl bromides at 60°C, affording the corresponding aryl amines in good to excellent yields. The active Cu catalyst was thoroughly characterized by UV-visible spectroscopy, x-ray photoelectron spectroscopy (XPS), and Electron Paramagnetic Resonance (EPR). It is worth noting that our current catalyst system shows better catalytic activity and selectivity than conventional organic solvents such as DMF, 1,4-dioxane, DMSO, and toluene. This study demonstrates that electronic, steric, and micellar cooperativity play decisive roles in aqueous copper-catalyzed reactions and establishes a practical, sustainable platform for C─N cross-coupling reactions.